Comparative Effects of Nebivolol and Metoprolol on Female Sexual Function

• Sponsor: East Coast Institute for Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00995072
• Collaborator: (none)
• Enrollment: 29
• Location: 1
• Arms: 2
• Duration (Months): 42
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Beta-blockers (BB) are an important treatment for high blood pressure and heart disease. However beta-blockers can cause sexual dysfunction (SD) and this common side effect limits successful use of this class of medications. Sexual side effects often result in drug discontinuation, compromising therapy goals. The investigators are conducting the study to determine if nebivolol, a newer beta blocker that is selective for receptors in the heart and causes vasodilation in the body causes fewer sexual side effects, or even improves sexual function, compared with metoprolol succinate.

Condition or Disease	Intervention/Treatment	Phase
Hypertension; Female Sexual Dysfunction	Drug: nebivolol and metoprolol succinate; Drug: metoprolol succinate and nebivolol	N/A

Detailed Description

This protocol is designed to compare the effects two beta blockers, nebivolol (Bystolic) 5-10 mg daily with metoprolol succinate (Toprol XL) 100-200 mg daily on sexual function in post-menopausal women with high blood pressure. The study is composed of 2 treatment phases. At baseline subjects are randomized to either nebivolol 5 mg once daily or metoprolol succinate 100 mg once daily. After randomization, subjects are treated for 12 weeks with double blind therapy. Following double-blind therapy subjects enter a 2-week washout phase and are subsequently switched to the alternate therapy.

After 4 weeks (visits 3 and 7) of double-blind treatment with either nebivolol 5 mg once daily or metoprolol succinate 100 mg once daily subjects will be evaluated and the need for dosage titration assessed. If blood pressure is not at goal the dosage of study medication will be doubled to nebivolol 10 mg once daily or metoprolol succinate 200 mg once daily. If blood pressure remains uncontrolled after 8 weeks of double blind treatment with study medication open label amlodipine 5 mg will be initiated (visits 4 and 8) at the discretion of the principal investigator. During double blind treatment subjects will be evaluated in clinic every 4 weeks.

The primary efficacy variable is the change from baseline in Changes in Sexual Functioning Questionnaire (CSFQ) and the Female Sexual Function Index (FSFI).

The primary study objective is to determine whether nebivolol causes fewer sexual side effects compared with metoprolol succinate and if nebivolol improves FSF in women. FSF will be assessed with the above questionnaires-FSFI and CSFQ.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparative Effects of Nebivolol and Metoprolol on Female Sexual Function
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Nebivolol 5 mg daily for 12 weeks followed by Metoprolol succinate 100 mg daily for 12 weeks. A two week washout (no medication) is completed prior to switching to metoprolol.	Drug: nebivolol and metoprolol succinate; Subjects randomized to treatment Arm A will receive nebivolol 5 mg once daily for 12 weeks. After 12 weeks, double blind therapy will be discontinued and patients will undergo a wash-out period of study therapy over 2 weeks. Subjects randomized to treatment Arm A will then receive metoprolol succinate 100 mg once daily. Subjects will continue double blind therapy for a total duration of 12 weeks.; Other Names: nebivolol Bystolic metoprolol succinate Toprol XL
Experimental: Arm B Metoprolol succinate 100 mg daily for 12 weeks followed by nebivolol 5 mg daily for 12 weeks. A two week washout (no medication) is completed prior to switching to nebivolol.	Drug: metoprolol succinate and nebivolol; Subjects randomized to treatment Arm B will receive metoprolol succinate 100mg once daily for 12 weeks. After 12 weeks, double blind therapy will be discontinued and patients will undergo a wash-out period of study therapy over 2 weeks. Subjects randomized to treatment Arm B will then receive nebivolol 5 mg once daily. Subjects will continue double blind therapy for a total duration of 12 weeks.; Other Names: nebivolol Bystolic metoprolol succinate Toprol XL

Outcome Measures

Primary Outcome Measures

1. Change in Female Sexual Function Index [Baseline, 12 weeks]

   This scale is a self-reported instrument used to detect female sexual function. The scale ranges from 2 to 36. The higher score indicates higher sexual function.

Secondary Outcome Measures

1. Change in Sexual Functioning Questionnaire Score [Baseline, 12 weeks]

   This scale is a self-reported instrument used to detect sexual functioning. The scale ranges from 14 to 70. The higher scores reflects higher sexual functioning.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Over the age of 40 years

2. Postmenopausal (according to self report of 12 consecutive months of amenorrhea, serum FSH concentrations greater than 40 international units/L, or surgical history consistent with menopause)

3. In a stable monogamous relationship with a male partner for at least 6 months

4. History of hypertension, treated or untreated

5. Requirement for the initiation of an anti-hypertensive agent OR addition of another anti-hypertensive medication (according to the principal investigator and based on clinical judgment) OR patients requiring monotherapy with an anti-hypertensive that wish to participate in the study and are willing to undergo a two week wash-out of current anti-hypertensive therapy

6. Provide written informed consent prior to participation.

Exclusion Criteria:

1. Properly measured clinic SBP > 170 mmHg

2. Advanced AV block

3. Severe hepatic disease

4. Heart rate < 55 beats/min (and not currently on beta blocker therapy)

5. Pregnancy or lactation

6. Heart failure with ejection fraction less than 0.40

7. History of myocardial infarction

8. History of Raynaud's syndrome

9. Patients with alcoholism or recreational drug use will be excluded due to concerns about the ability to comply with the study requirements.

10. Major psychiatric disorder not well controlled with treatment

11. Spinal cord injury

12. Severe respiratory disease, which in the opinion of the investigator contraindicates BB treatment

13. Poorly controlled diabetes mellitus (≥ 9%)

14. Persistent arrhythmia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Family Practice	Jacksonville	Florida	United States	32204

Sponsors and Collaborators

• East Coast Institute for Research

Investigators

• Principal Investigator: Benjamin Epstein, PharmD, East Coast Institute for Research

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Benjamin Epstein, Principal Investigator, East Coast Institute for Research
• ClinicalTrials.gov Identifier: NCT00995072
• Other Study ID Numbers: SAIRB-09-0011
• First Posted: Oct 14, 2009
• Last Update Posted: Mar 29, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Benjamin Epstein, Principal Investigator, East Coast Institute for Research: sexual dysfunction; female; hypertension; high blood pressure; beta blockers; metoprolol; nebivolol; Bystolic; Toprol XL
• Additional relevant MeSH terms: Hypertension; Metoprolol; Nebivolol

Study Results

Participant Flow

Pre-assignment Detail	4 subjects were randomized and dropped from the study prior to taking the study medication

Arm/Group Title	Nebivolol 5 mg Daily First, Then Metoprolol Succinate 100 mg	Metoprolol Succinate 100 mg First, Then Nebivolol 5 mg Daily
Arm/Group Description	Nebivolol 5 mg daily for 12 weeks followed by Metoprolol succinate 100 mg daily for 12 weeks. A two week washout (no medication) is completed prior to switching to metoprolol. nebivolol and metoprolol succinate: Subjects randomized to treatment Arm A will receive nebivolol 5 mg once daily for 12 weeks. After 12 weeks, double blind therapy will be discontinued and patients will undergo a wash-out period of study therapy over 2 weeks. Subjects randomized to treatment Arm A will then receive metoprolol succinate 100 mg once daily. Subjects will continue double blind therapy for a total duration of 12 weeks.	Metoprolol succinate 100 mg daily for 12 weeks followed by nebivolol 5 mg daily for 12 weeks. A two week washout (no medication) is completed prior to switching to nebivolol. metoprolol succinate and nebivolol: Subjects randomized to treatment Arm B will receive metoprolol succinate 100mg once daily for 12 weeks. After 12 weeks, double blind therapy will be discontinued and patients will undergo a wash-out period of study therapy over 2 weeks. Subjects randomized to treatment Arm B will then receive nebivolol 5 mg once daily. Subjects will continue double blind therapy for a total duration of 12 weeks.
Period Title: Overall Study
STARTED	10	15
COMPLETED	9	12
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Nebivolol 5 mg Daily First, Then Metoprolol Succinate 100 mg	Metoprolol Succinate 100 mg First, Then Nebivolol 5 mg Daily	Total
Arm/Group Description	Nebivolol 5 mg daily for 12 weeks followed by Metoprolol succinate 100 mg daily for 12 weeks. A two week washout (no medication) is completed prior to switching to metoprolol. nebivolol and metoprolol succinate: Subjects randomized to treatment Arm A will receive nebivolol 5 mg once daily for 12 weeks. After 12 weeks, double blind therapy will be discontinued and patients will undergo a wash-out period of study therapy over 2 weeks. Subjects randomized to treatment Arm A will then receive metoprolol succinate 100 mg once daily. Subjects will continue double blind therapy for a total duration of 12 weeks.	Metoprolol succinate 100 mg daily for 12 weeks followed by nebivolol 5 mg daily for 12 weeks. A two week washout (no medication) is completed prior to switching to nebivolol. metoprolol succinate and nebivolol: Subjects randomized to treatment Arm B will receive metoprolol succinate 100mg once daily for 12 weeks. After 12 weeks, double blind therapy will be discontinued and patients will undergo a wash-out period of study therapy over 2 weeks. Subjects randomized to treatment Arm B will then receive nebivolol 5 mg once daily. Subjects will continue double blind therapy for a total duration of 12 weeks.	Total of all reporting groups
Overall Participants	9	12	21
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 88.9%	9 75%	17 81%
>=65 years	1 11.1%	3 25%	4 19%
Sex: Female, Male (Count of Participants)
Female	9 100%	12 100%	21 100%
Male	0 0%	0 0%	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
United States	9 100%	12 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	Change in Female Sexual Function Index
Description	This scale is a self-reported instrument used to detect female sexual function. The scale ranges from 2 to 36. The higher score indicates higher sexual function.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The number of participants analyzed for the measure are participants that had data available for both of the study periods.

Arm/Group Title	Nebivolol 5 mg Daily	Metoprolol Succinate 100 mg Daily
Arm/Group Description	Nebivolol 5 mg daily for 12 weeks	Metoprolol succinate 100 mg daily for 12 weeks
Measure Participants	15	15
Mean (Standard Deviation) [units on a scale]	1.24 (9.183)	1.42 (5.262)

2. Secondary Outcome

Title	Change in Sexual Functioning Questionnaire Score
Description	This scale is a self-reported instrument used to detect sexual functioning. The scale ranges from 14 to 70. The higher scores reflects higher sexual functioning.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The number of participants analyzed for the measure are participants that had data available for both of the study periods.

Arm/Group Title	Nebivolol 5 mg Daily	Metoprolol Succinate 100 mg Daily
Arm/Group Description	Nebivolol 5 mg daily for 12 weeks	Metoprolol succinate 100 mg daily for 12 weeks
Measure Participants	13	13
Mean (Standard Deviation) [units on a scale]	2.38 (7.600)	0.85 (8.315)

Adverse Events

Adverse Event Reporting Description	Adverse Events were collected but the data were destroyed and are not available for reporting.
Arm/Group Title	Nebivolol 5 mg		Metoprolol Succinate 100 mg
Arm/Group Description	Nebivolol 5 mg daily		Metoprolol succinate 100 mg daily
All Cause Mortality
	Nebivolol 5 mg		Metoprolol Succinate 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)
Serious Adverse Events
	Nebivolol 5 mg		Metoprolol Succinate 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Nebivolol 5 mg		Metoprolol Succinate 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

The study had a lower than anticipated enrollment and a high drop-out rate due to loss of follow-up-although the drop-out rate was not unexpected based on the study population.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.